Engineering vascularized bone tissues by microfabrication and scaffolding Repair of craniofacial and other large bone defects remains a significant clinical problem. Often bone grafts are required for reconstructive skeletal procedures to aid fracture healing, bone fusion, implant integration and repair of skeletal defects, but the use of allograft bone is limited by a high failure rate. Tissue engineered constructs are promising substitutes. The major challenge of bone tissue engineering is the formation of a complete vascular network capable of delivering oxygen and nutrients and removing waste products that limits the maximum effective size of tissue engineered constructs. Most tissue engineering approaches rely on the self-assembly of cells to recreate functional vascularity on biodegradable scaffolds, but it rarely occurs. We therefore propose to construct bone tissues having a vascular network by (1) microfabricating and optimizing a vascular network with biomimetic complexity;(2) optimizing a synthetic bony environment to support the function of the microfabricated vascular networks;and (3) validating enhanced functionality of the developed vascularized bone tissue constructs in vivo. The success of this project will significantly advance the paradigm of vascular networks in engineered tissues by the creation of a vascularized bone construct prototype, with a long term goal of a new treatment in large bone defect repair in humans. PUBLIC HEALTH RELEVANCE: Repair of craniofacial and other large bone defects remains a significant clinical challenge. This project is expected to generate a new paradigm in bone tissue engineering by enabling the formation of a complete vascular network at a large scale by microfabrication and scaffolding.